(Clarifies drug name and manufacturer in para 1; clarifies in
para 3 that there were two separate studies; adds "crossover" to
para 4; adds new para 7.)

By David Douglas

NEW YORK (Reuters Health) - Delayed-release metformin (Met
DR; Elcelyx) is formulated to deliver drug to the lower bowel
and may curb the circulation-based side effects of other
formulations, according to a recent study.

"The American Diabetes Association and the European
Association for the Study of Diabetes recommend metformin as the
first-line treatment for type 2 diabetes patients, but there
isn't an equally effective oral treatment option for patients
with renal impairment who are unable to take the drug because of
accumulation in the circulation," co-author of the study, Dr.
Mark Fineman of Elcelyx Therapeutics in San Diego, California,
wrote in email to Reuters Health.

In phase 1 and phase 2 trials, reported in a single paper
online August 18 in Diabetes Care, Dr. Fineman and colleagues
compared the bioavailability and glycemic effect of Met DR to
that of immediate release metformin (Met IR) and
extended-release metformin (Met XR).

The randomized crossover study of 20 healthy volunteers in
Phase 1 found that the bioavailability of 1,000 mg Met DR
administered twice a day was about half that of Met IR and Met
XR.

In Phase 2, the researchers conducted a dose-ranging study
in 240 patients with type 2 diabetes.

After 12 weeks, the researchers found that compared to
placebo, all doses of Met DR produced "statistically
significant, clinically relevant, and sustained reductions" in
fasting plasma glucose (FPG).

After adjustment, changes from baseline HbA12 at 12 weeks
were consistent with changes in FPG levels.

Compared to Met XR, Met DR demonstrated about a 40% increase
in potency.

The investigators concluded that metformin primarily
restricted to the gut effectively lowers plasma glucose levels.
In fact, they added, "the gut contribution to glucose lowering
may be more important than systemic mechanisms."

"These clinical results provide strong evidence that
metformin works in the gut to lower glucose," Dr. Fineman told
Reuters Health. "As Metformin DR is engineered to principally
target the gut and not the circulation it may mitigate the risk
of metformin associated lactic acidosis."

"Based on these results," he concluded, "we are conducting
additional clinical trials to support development of this
important therapeutic option to patients with type 2 diabetes
and moderate renal impairment for whom metformin is currently
contraindicated."

This study was commissioned and funded by Elcelyx
Therapeutics. Four of the eight authors are employees of the
company.